For several decades, chemists have designed and synthesized organic molecules that bind to the active sites of proteins and inhibit protein functions. The fact that proteins adopt folded, three-dimensional structures with unique binding pockets allows chemists to develop small organic molecules that bind with high affinity and specificity to a target protein. Because RNA can also possess folded, three-dimensional structures, it should be possible for chemists to design new molecules that bind a target RNA with high affinity and specificity. Such molecules could ultimately evolve into new types of drugs that exert their biological effects by targeting RNA. Since the biophysical properties of RNA are very different from proteins, the types of molecules that must be developed for RNA binding will be very different from the molecules that bind to proteins. Currently, RNA is significantly underutilized as a potential target for drug development: most likely because there exists a lack of basic knowledge about how one should design a molecule to target a folded RNA. In our research, the RNA-binding properties of sidechain-functionalized polyamines are being examined with two important RNA targets: TAR RNA and RRE RNA of HIV. Molecules that bind to these RNAs can potentially shut down replication of the virus. The basic knowledge that will be developed from this work will ultimately be applicable to other RNA targets, and will provide a general set of guidelines for designing molecules that selectively bind a folded RNA structure. Over the past year, we have established a new library of molecules that can be screened for selective binding to TAR RNA, and we have validated this screening strategy using a number of basic biochemical methods. We are currently optimizing our initial leads for better binding affinity, and we are trying to initiate a collaboration with cell biologists to study the activity of these molecules in HIV infected cells.